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Molecular mechanisms of GDF11 and MSTN signaling The mature GDF11 and MSTN ligands first bind to activin type 2 receptors (ACVR2A or ACVR2B) and subsequently recruit type 1 receptors, activin receptor-like kinase 4 (ALK4) or ALK5 to form a heteromeric receptor complex to elicit downstream signaling via phosphorylation of SMAD2 and/or SMAD3 (Fig

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